Science1 publisher2 min readPublished
Deleting the SK3 channel from serotonin neurons curbs craving behavior in pregnant mice
In mice, pregnancy turns up an SK3 potassium channel that quiets dorsal raphe serotonin neurons and raises the pull of palatable food. The team tested the channel in both directions before tracing its path to the reward system.
The Scientist · Science desk
What happened
- Electrophysiological recordings in pregnant mice found dorsal raphe serotonin neurons firing more slowly at baseline, alongside escalated eating of palatable food, in a study published in Nature Neuroscience.
- The team tied that quieting to the SK3 potassium channel, and deleting SK3 from serotonin neurons kept firing rates normal through gestation while substantially reducing craving-like behavior.
- Artificially raising SK3 activity in nonpregnant female mice reproduced both the drop in firing and the craving behavior that pregnancy normally produces.
- Stimulating the traced dorsal raphe to ventral tegmental area pathway curbed food-seeking in pregnant animals, and silencing it in nonpregnant controls was enough to provoke cravings.
- The work was led by Yanlin He at LSU's Pennington Biomedical Research Center with Pingwen Xu at the University of Illinois Chicago and Chunmei Wang at Baylor College of Medicine.
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Why it matters
- capability Pregnancy craving behavior can now be switched on and off in a mouse at two levels of one pathway. Whether the quieting of serotonin neurons does anything useful for gestation is the next question.
- constraint The endpoint is intake and seeking of palatable food in rodents. The food-specific, time-specific wanting that people describe in pregnancy sits outside what this design can address.
- exposure Cravings sit upstream of gestational diabetes and maternal obesity. A target here would be aimed at outcomes in two patients at once, and it would have to clear a safety bar set by both.
- precedent Four manipulations: delete the channel, add the channel, drive the tract, silence the tract.
SK3 is a small-conductance calcium-activated potassium channel, and it works as a brake. Open channels let potassium leave the cell, the membrane hyperpolarizes, and fewer action potentials get out [4]. The dorsal raphe is a brainstem region dense with serotonin neurons that help set mood, appetite and satiety [12]. A channel that sets the excitability of those cells is a reasonable place to look for a pregnancy effect on eating.
A firing rate that falls at the same time as eating rises could be a result of the eating. The knockout rules that out: take the channel out of serotonin neurons and the firing rate holds through gestation, and most of the craving-like behavior goes with it [5]. The opposite experiment tests it from the other side. In a nonpregnant female mouse, elevated SK3 activity is the only pregnancy-like change in play, and it eats like a pregnant one anyway [6].
In the account given by the researchers, serotonin output normally keeps reward-seeking in check, and lifting that inhibitory tone lets the ventral tegmental area amplify the pull of highly palatable food [15]. The projection they traced runs from dorsal raphe serotonin neurons onto the VTA, and it is inhibitory [7]. Count the experiments and there are four manipulations, arranged as two pairs that push in opposite directions at two levels of one pathway [13].
According to the summary from LSU's Pennington Biomedical Research Center, excessive cravings can contribute to gestational diabetes, maternal obesity and longer-term metabolic complications for both parent and child [9]. What pregnancy signal turns SK3 up in the first place is left to later work.
In a rodent study, craving is an inference from what the animal eats. What was measured is intake of and seeking for palatable food [2][8]; a mouse cannot report wanting one particular food at two in the morning. The write-up does not include firing rates, animal numbers or the size of the behavioral change [14], and the authors caution about direct clinical application of the findings [11].
What to watch
- Whether an independent lab reproduces the SK3 gain-of-function result in nonpregnant female mice.
- Which pregnancy signal raises SK3 activity in the first place, and whether it is hormonal.
- Whether manipulating the DRN-to-VTA projection moves maternal glucose and weight gain, not only food-seeking.